Clinical data suggest that evaluated angiotensin-11 (A-11) or renin levels in plasma of hypertensive subjects are associated with an increased risk of myocardial infarction and cerebro-vascular accidents. Ultrastructural and permeability studies in hypertension indicate that there is regional variation in the response of the circulatory system to the hypertensive state. Observations made in this laboratory provide strong evidence that the regional response of the arterial vasculature to hypertension (hyalinosis, hyperplasia, fibrinoid change and medial necrosis) is primarily a consequence of elevated filling tension and a direct vasculo-necrotic action of A-11. Permeability changes in the vasculature appear to be mediated, at least in part, by contraction of endothelial cells. The long term goal of our research program has been and remains a better understanding of the morphogenesis of hypertensive vascular disease. The present proposal specifically aims: 1) to define the origin and composition of vascular hyalin at the cellular level by labeling studies, radioautography and enzyme digestion; 2) to identify the endothelial proteins responsible for the contraction of arterial endothelium in hypertension by immunohistology (fluorescein and peroxidase labeled antibodies) and electron microscopy (immuno- peroxidase technique); 3) to relate regional variation primarily to the interplay between effects of elevated filling tension and a direct vasculo-necrotic action of A-11 on arterial vasculature, utilizing a combination of electron microscopy, circulating probe molecules, and experimental vascular surgery. The models of hypertension to be employed are unilateral renal artery constriction in the rat with contralateral kidney in place, and acute hypertension produced by continuous infusion of A-11.